Interstitial Cystitis(IC) is a complex of symptoms without an etiology, and thus a 'disease' without a cure. Methodologies such as statistical data management, and parallel mast cell quantification and immunohistochemical analysis of leukocytes in bladder biopsies of IC and Non-IC patients, have been unsatisfactory, because they have been non- heuristic. Studies of bladder mucosal integrity using standard cystometric methodology have stimulated more questions about the dynamic characteristics of the bladder and its mucosal complex [i.e. urothelium, lamina propria and the incompletely studied 'suburothelial capillary plexus'(SCP)]. The urothelium has been studied extensively over the years, but other elements of the mucosa have been but briefly mentioned in the literature. It is our view that the urothelium, the primary interface between urine and bladder wall; the lamina propria, the primary structural element of the mucosa; and the SCP, the vascular component of the mucosa deserve to be considered as a functional unit. More particularly, a specific long-term goal is to elucidate a mechanistic explanation of the effect of gender on mucosal integrity, especially in light of the unexplained sex bias of 'diseases' such as IC. A long-term, but specific goal of this investigation is to better understand the functional and structural characteristics and limits of all of the components of the bladder mucosa. Considered to be a primary mediator of IC, we will use standard cystometric methods and dye indicators of mucosal integrity such as Trypan Blue to test the integrity of each of the mucosal components. The short-term goals are: 1) to compare the integrity of the bladder mucosae in age-matched male and female rabbits. We propose to coordinate and correlate in vivo cystometry with chemical, physiologic, anatomic, histologic, and ultrastructural methods of analysis. In parallel, we propose to initiate an dynamic study of the anatomy of the SCP, first as a function of volume and then of the rate of instillation. 2) Second, we will investigate the integrity of the mucosae of age-matched males and females when exposed to acid and basic dyes of similar mass, a lysochrome, and neutral dextrans ranging in molecular weight from 4-5OOk. 3) Third, we propose to study the effects of volume and rate on age-matched groups of castrated, males (treated with testosterone) and ovariectomized females (treated with estradiol or progesterone) to elucidate gender-based differences in mucosal behavior related to sex hormones. 4) Finally, we propose to study both the mucosa in general and the SCP in particular during the period of functional recovery following unilateral ischemia.